Temporomandibular joint pain: A critical role for Trpv4 in the trigeminal ganglion

Chen, Yong; Williams, Susan H.; McNulty, Amy L.; Hong, Ji Hee; Lee, Suk Hee; Rothfusz, Nicole E.; Parekh, Puja K.; Moore, Carlene; Gereau, Robert W.; Taylor, Andrea B.; Wang, Fan; Guilak, Farshid; Liedtke, Wolfgang

doi:10.1016/j.pain.2013.04.004

Cited by 104 publications

(131 citation statements)

References 48 publications

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“…4E). Moreover, when a selective TRPV4 blocker, GSK205 (43,58,59), was used, WT 1°MK showed responses similar to those of Trpv4 −/− 1°MK (Fig. 4F).…”

Section: Trpv4 Sustains the Uvb-induced Ca 2+ Response In Primary Mousementioning

confidence: 84%

“…S1D). Interestingly, whereas sensitization could be verified in control mice, it was absent in tam-treated iKO mice, as documented by labeling for phosphorylated ERK (pERK), a known marker of sensory neuron activation in response to inflammation and irritation (43,55) (Fig. 1E).…”

Section: Activation Markers Of Skin-innervating Peripheral Neurons Sumentioning

confidence: 94%

“…For pathological pain, it is relevant for inflammation-and nerve-damage-induced pain sensitization (41)(42)(43). Of note, Trpv4 −/− mice exhibit impaired skin-…”

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confidence: 99%

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UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

Moore¹,

Cevikbas

Pasolli³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Skin protects against harmful external cues, one of them UV radiation, which, upon overexposure, causes sunburn as part of the UVB response. Using genetically engineered mice and cultured skin epithelial cells, we have identified the calcium-permeable TRPV4 ion channel in skin epithelial cells as critical for translating the UVB stimulus into intracellular signals and also into signals from epithelial skin cell to sensory nerve cell that innervates the skin, causing pain. These signaling mechanisms underlie sunburn and in particular sunburn-associated pain. Thus, activation of TRPV4 in skin by UVB evokes sunburn pain, highlighting the forefront-signaling role of the skin and TRPV4.

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“…4E). Moreover, when a selective TRPV4 blocker, GSK205 (43,58,59), was used, WT 1°MK showed responses similar to those of Trpv4 −/− 1°MK (Fig. 4F).…”

Section: Trpv4 Sustains the Uvb-induced Ca 2+ Response In Primary Mousementioning

confidence: 84%

Section: Activation Markers Of Skin-innervating Peripheral Neurons Sumentioning

confidence: 94%

See 1 more Smart Citation

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

Moore¹,

Cevikbas

Pasolli³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

223

207

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“…For cartilage, knee and hip cartilage (n = 3 samples; each sample contained pooled tissues from three to four mice) was harvested and stored in RNA-later (Life Technologies) until RNA extraction. Total RNA was extracted for subsequent RT-qPCR, as described previously (73)(74)(75). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a housekeeping gene for normalization, and expression in lung was defined as "1."…”

Section: Methodsmentioning

confidence: 99%

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

Lee¹,

Leddy²,

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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367

348

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Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca 2+ signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca 2+ transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1-or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.A rticular cartilage is a hydrated connective tissue that supports loads and minimizes friction in the diarthrodial joints. It has a highly differentiated extracellular matrix (ECM) composed primarily of type II collagen, the large aggregating proteoglycan, aggrecan, and water. Chondrocytes are the only cells in cartilage and are responsible for maintaining and remodeling cartilage through a homeostatic balance of anabolic and catabolic activities. Under normal physiologic conditions, chondrocytes are exposed to millions of cycles of mechanical loading per year (1). These mechanical signals play an important role in regulating chondrocyte anabolic and biosynthetic activity, as evidenced by cartilage atrophy following periods of disuse or immobilization (2-7). However, under abnormal loading conditions (e.g., due to obesity, trauma, or joint instability), mechanical factors play a critical role in the onset and progression of osteoarthritis (1). Such "injurious" loading has been modeled in vitro using explant culture systems that replicate many of the early cellular and molecular events characteristic of osteoarthritis (8). Osteoarthritis is a painful and debilitating disease of weight-bearing joints that affects over 26 million people in the United States (9) with posttraumatic arthritis being responsible for ∼12% of the incidence of osteoarthritis (10).Despite the critical importance of mechanical loading in health and disease of synovial joints, the mechanisms of mechanotransduction of chondrocytes are not fully understood and are likely to differ under physiologic and pathologic conditions (11)(12)(13)(14). Although many different mechanisms have been shown to be involved in chondrocyte mechanotransduction (13,(15)(16)(17), recent st...

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“…Of note, both subfamilies have been linked to pain signalling and are known to conduct Ca 2+ (refs 5, 15, 24, 25). Most of these channels show an increased selectivity for Ca 2+ over Na + (refs 1, 16, 26, 27, 28), presumably as a function of the selectivity filter.…”

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confidence: 99%

TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour

et al. 2014

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Animals need to sense and react to potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca2+ influx, in most animal species. However, the relationship between ion permeation and animals’ nocifensive behaviour is unknown. Here we use an invertebrate animal model with relevance for mammalian pain. We analyse the putative selectivity filter of OSM-9, a TRPV channel, in osmotic avoidance behaviour of Caenorhabditis elegans. Using mutagenized OSM-9 expressed in the head nociceptor neuron, ASH, we study nocifensive behaviour and Ca2+ influx. Within the selectivity filter, M601-F609, Y604G strongly reduces avoidance behaviour and eliminates Ca2+ transients. Y604F also abolishes Ca2+ transients in ASH, while sustaining avoidance behaviour, yet it disrupts behavioral plasticity. Homology modelling of the OSM-9 pore suggests that Y604 may assume a scaffolding role. Thus, aromatic residues in the OSM-9 selectivity filter are critical for pain behaviour and ion permeation. These findings have relevance for understanding evolutionary roots of mammalian nociception.

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Temporomandibular joint pain: A critical role for Trpv4 in the trigeminal ganglion

Cited by 104 publications

References 48 publications

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour

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